I. Field of the Invention
The present invention relates to the synthesis and use of a novel derivative of L-ascorbic acid. This derivative of L-ascorbic acid includes cholesterol. The resultant product is stable, easily incorporated into cosmetically acceptable vehicles and enzymatically bioreversible.
II. Description of the Prior Art
The use of L-ascorbic acid as an antioxidant in food preparations is known. For example, Steinhart, Pro- and Antioxidative Effect of Ascorbic Acid on L-Tryptophan in the Fe3+/Ascorbic Acid/O, J. Agric. Food Chem., Vol. 41, pages 2275-2277 (1993) describes the use of L-ascorbic acid as an antioxidant that functions in food to remove free radicals and undergoing rapid oxidation.
Similarly, free L-ascorbic acid in topical preparations demonstrates poor stability and tends to break down due to partially oxidative and non-oxidative degradation. The degraded ascorbic acid loses activity and the resultant product loses aesthetic appeal since it exhibits a cosmetically undesired brown color.
While cholesterol is considered unhealthy especially when ingested, the benefits of cholesterol, necessitated with L-ascorbic acid, for skin barrier repair are known. For example, Menon, Structural Basis for the Barrier Abnormality Following Inhabitations of HMG CoA Reductase in Murine Epidermis, J. Invest. Dermatol., Vol. 98, pages 209-219 (1992), describes deficiencies in the skin barrier repair mechanism when cholesterol synthesis is inhibited by regulation of HMG CoA reductase.
Presently, mechanical mixing of L-ascorbic acid and cholesterol results in an unstable product due to the instability of L-ascorbic acid. For example, U.S. Pat. No. 4,939,128 to Kato is directed to the use of phosphoric acid esters of ascorbic acid for the treatment of diseases, not for cosmetics, topical dermatological or skin uses, and teaches that certain phosphoric acid esters of ascorbic acid display improved oxygen scavenging properties. One of the phosphoric acid esters in the patent is substituted with a cholestanyl group. The conspicuous absence of cholesterol and the specific mention of a cholesteryl group recognizes that conjugates of L-ascorbic acid and cholesterol were then not practical or desired.
Attempts have been made to conjugate ascorbic acid with a glycyrrhetic group as described in European Application No. 92104149.7; and with a tocopheryl group as indicated by U.S. Pat. No. 3,151,127. U.S. Pat. Nos. 4,564,686 and 5,306,713 disclose tocopheryl ascorbyl phosphate as an anti-oxidant having the following structure: ##STR1##
Also, Sakamoto, Measurement Method of Efficacy of Antidandruff Cosmetics and Development of the New Active Commercial Product, IFSCC, Yokohama, Vol. B206, pages 823-864 (1993) describes the use of tocopheryl coupled to L-ascorbic acid. The coupled tocopheryl is an antioxidant preservative for the ascorbyl group, but the use of the ascorbyl-tocopheryl as a skin therapeutic is questionable since, unlike cholesterol, tocopheryl is not a natural substrate for the skin.
Heretofore, there has been needed a stable product having cholesterol coupled to L-ascorbic acid, which product retained full functional activity even after decoupling by naturally occurring acidic phosphatases in the skin. This product would provide the beneficial properties of L-ascorbic acid, including increased collagen production and skin-lightening, combined with the benefits of released cholesterol, namely improved elasticity, resistance, tone and moisture retention of the skin. Accordingly, there has been needed a method for covalently and bioreversibly effecting the coupling of cholesterol to L-ascorbic acid.